Arsenic (As) exposure is associated with cancer, lung and cardiovascular disease, yet the mechanisms involved are not clearly understood. Elevated matrix metalloproteinase-9 (MMP-9) levels are also associated with these diseases, as well as with exposure to water As. Our objective was to evaluate the effects of dietary components of inorganic As (iAs) intake on serum MMP-9 concentration at differing levels of tap water As. In a cross-sectional study of 214 adults, dietary iAs intake was estimated from 24-h dietary recall interviews using published iAs residue data; drinking and cooking water As intake from water samples and consumption data. Aggregate iAs intake (food plus water) was associated with elevated serum MMP-9 in mixed model regression, with and without adjustment for covariates. In models stratified by tap water As, aggregate intake was a significant positive predictor of serum MMP-9 in subjects exposed to water As≤10 μg/l. Inorganic As from food alone was associated with serum MMP-9 in subjects exposed to tap water As≤3 μg/l. Exposure to iAs from food and water combined, in areas where tap water As concentration is ≤10 μg/l, may contribute to As-induced changes in a biomarker associated with toxicity.

Les expositions professionnelles agricoles, et notamment l’exposition aux pesticides, ont été associées à divers effets négatifs, sur la fertilité, le déroulement de la grossesse et le développement de l’enfant. Peu d’études se sont intéressées à des activités agricoles spécifiques excepté le travail sous serre et la floriculture et aucune n’a été à ce jour conduite en France. (1) L’interrogation de plus de 800 femmes, incluses dans la cohorte AGRIculture & CANcer (AGRICAN) et ayant eu une grossesse depuis l’inclusion (2005), grâce à 2 questionnaires rétrospectifs a montré un allongement du délai nécessaire à concevoir en lien avec l’emploi sur une exploitation agricole, le travail de nuit ou l’exposition à des vibrations. Des augmentations de risque d’avortements spontanés et de malformations ont également été observées mais restent à confirmer. (2) Le développement d’une méthode d’analyse multi-résidus a permis de mesurer 25 pesticides différents parmi 116 recherchés dans les urines de femmes travaillant sur des exploitations de poly-culture élevage. Les herbicides étaient les plus fréquemment détectés, notamment en lien avec la présence de maïs sur l’exploitation ou de tâches réalisées au contact des animaux d’élevage. Le glyphosate ou son métabolite AMPA étaient retrouvés dans 85% des échantillons.Un projet de recherche poursuivra les travaux engagés en s’intéressant au développement cognitif des enfants nés depuis 2005. / Agricultural exposures, including pesticide exposure, have been associated with several negative effects on fertility, pregnancy and child development. Few studies focused on specific agricultural activity excepted floriculture and working in greenhouse and none was conducted in France. (1) More than 800 women, enroled in the AGRIculture & CANcer (AGRICAN) cohort and who reported a pregnancy since enrolment (2005) agreed to fill in 2 questionnaires. An increase of time to pregnancy was observed for women who worked on a farm, for those exposed to night work and to vibrations. Increased risks of spontaneous abortions or abnormalities were also observed in relation to agricultural work but these results need to be confirmed. (2) Multi-residue analytical method was developed and applied to women of childbearing age, working in crop-livestock farms. Twenty-five pesticides or metabolites were detected among 116 measured in urine samples. Herbicides were the most frequently detected, especially when women worked on corn-crop farms or were involved in breeding tasks. Glyphosate or its metabolite AMPA were detected in 85% of urine samples.Future project will allow us to investigate cognitive development of children born since 2005.

Masters of Art / This study examines the effects of domestic violence on adults who witnessed abuse as children in their homes. It seeks to ascertain if the childhood emotional trauma of domestic violence influences the growth and social adaptation of children in their later years. Despite the growing awareness of domestic violence worldwide, there is nevertheless an alarming number of women reporting abuse, and there are those who are reportedly beaten or inflicted with bodily harm at the hands of their abusers. However, most of these domestic or household conflicts take place in situations where children are involved. These children witness such abuse and grow up carrying emotional and physical scars that impact their functioning as members of society. The study adopts a life history approach to investigate 15 adult participants (five women and ten men) within evolving themes relating to their experiences of domestic violence and other life ordeals during their childhood that made them end up at the Elim Night Shelter in Cape Town, South Africa. The study is anchored on the explication of such key concepts as domestic violence, abuse and the physical, social, emotional and behavioural effects of abuse. Furthermore, the study identifies the social consequences of growing up in an abusive environment. The findings of the study reveal that people who witnessed acts of domestic violence as children experience negative consequences as adults. Recommendations have been listed which could assist the further study expansion on the topic, together with intervention strategies.

No description available.

The parietal lobe has been shown to be one of the regions most affected by prenatal alcohol exposure. Functional domains dependent on intact parietal functioning, including mathematical and visuospatial ability, have been consistently implicated in fetal alcohol spectrum disorders. This thesis examines, in children, using blood oxygenation level dependent (BOLD) functional Magnetic Resonance Imaging, the effect of prenatal alcohol exposure on brain activation during symbolic and nonsymbolic number processing, and place learning in a virtual environment. These functional domains were investigated using tasks of proximity judgment and exact addition to assess neural correlates of symbolic number processing in 65 children (mean age ± SD = 9.45 ± 0.42 years), nonsymbolic number comparison at varying difficulties in 34 children (11.55 ± 1.15 years), and place learning in a virtual reality computer generated (CG) arena in 57 children (9.44 ± 0.42 years; 29 boys). In the symbolic number processing tasks greater prenatal alcohol exposure was related to less activation in the right horizontal intraparietal sulcus known to mediate mental representation and manipulation of quantity. Children with fetal alcohol syndrome and partial fetal alcohol syndrome appeared to compensate for this deficit by increased activation of the left angular gyrus during the proximity judgment task. Syndromal children with fetal alcohol syndrome or partial fetal alcohol syndrome also demonstrated poor recruitment of the right horizontal intraparietal sulcus during nonsymbolic number comparison, indicating that mental representation and manipulation of quantity are impaired in children with heavy prenatal alcohol exposure, irrespective of the representation format used. This impairment was compensated for by the left angular gyrus, with only exposed children needing to recruit the left angular gyrus to a greater extent as number comparison task difficulty increased. Further, reduced activation of the right posterior superior parietal lobule in children with increasing prenatal alcohol exposure suggests that exposed children may be less able to employ the attentional systems associated with number processing. Notably, activation of nonsyndromal heavily exposed children was impaired in the right posterior superior parietal lobule, but spared in the right horizontal intraparietal sulcus. In boys only, prenatal alcohol exposure was associated with poorer place learning and reduced activation during place learning in the precuneus and posterior cingulate, as well as parahippocampal gyrus, frontal and temporal lobes, caudate, insula, claustrum, lentiform nucleus and thalamus. In girls, prenatal alcohol exposure was not associated with place learning performance or activation during place learning in any regions. These results confirm that boys and girls use different navigation strategies that rely on different brain regions and suggest that the regions used by boys are more susceptible to alcohol damage, while the regions used by girls are relatively spared. In conclusion, all the tasks investigated showed prenatal alcohol exposure related alterations in parietal function, with the impairments being widespread throughout the parietal lobe bilaterally. Notably, activation of the bilateral precuneus was affected by prenatal alcohol exposure in both the spatial navigation and nonsymbolic number comparison tasks. It is possible that this is a key region linking the deficits in number processing and visuospatial skills in children with prenatal alcohol exposure.

Prenatal methamphetamine exposure is associated with functional and neurostructural alterations, but neuroimaging investigations of these effects in infants are almost non-existent. Studies in neonates permit a degree of separation of drug exposure effects from potential confounders in the postnatal environment. Magnetic resonance imaging (MRI) was used to investigate the neurostructural effects of prenatal methamphetamine exposure on neonates recruited from a Cape Town community. Mothers were recruited during pregnancy and interviewed regarding methamphetamine use. Women in the exposure group used methamphetamine at least twice per month during pregnancy, while control mothers did not use methamphetamine. MRI scans were acquired within the first postnatal month. Anatomical images were processed using FreeSurfer and subcortical and cerebellar structures manually segmented with Freeview. Volumes were regressed with methamphetamine exposure (days/month of pregnancy) and related confounding variables, including total brain volume, gestational age at scan, exposure to cigarette smoking and infant sex. Diffusion data were processed with FSL, and diffusion tensors and tensor parameters determined using AFNI. Probabilistic tractography defined white matter connections between target regions. For the first analysis, five major white matter networks (commissural, and bilateral projection and association networks) were defined between spherical targets. For the second analysis, regions traced in the anatomical study were used as targets. Averaged DTI parameters were then calculated for each connection, and multiple regression analysis determined associations between DTI parameters and methamphetamine exposure at network level and in the individual connections. Methamphetamine exposure was associated with reduced caudate nucleus volume bilaterally, and in the right caudate following adjustment for confounders. Exposure was associated with reduced fractional anisotropy in all major white matter networks, and in individual connections within the limbic meso-cortico-striatal circuit. Exposure was associated with increased radial diffusivity in a subset of these. These results support findings in older children of methamphetamine-induced neurostructural damage, and demonstrate that such effects are already measurable in neonates. Corticostriatal circuit changes may underlie the impaired executive function observed in prenatally exposed children, and suggest a specific mechanism of damage in dopaminergic-related circuits that is consistent with the neurotoxic actions of methamphetamine.

This project examined the extent to which psychosocial or personal variables moderated the relationship between exposure to violence and use of violence in adolescents. The relationship between exposure to violence and use of violence was examined within a sample of adolescents, ages 13 -18. The major goals of this study were to examine some possible correlates of violence use and to determine the extent to which certain personal variables (i.e., locus of control, social skills, feelings of despair, and certainty of being alive at age 25) operate as protective or vulnerability factors for those adolescents at risk for violence. The conceptualization of this study was based on the framework of the compensatory and protective vs. vulnerability models. As hypothesized, a strong relationship between exposure to community violence and use of violence was found in this study. In addition, level of despair was also correlated with use of violence. No relationship was found between use of violence and the following variables: exposure to domestic violence, certainty of being alive at age 25, social skills, or locus of control. Further, none of the psychosocial variables tested in this study were found to moderate the relationship between use of violence and exposure to domestic and community violence combined. However, when exposure to community and domestic violence were analyzed separately, two interaction effects were found. Social skills did appear to have a slight moderating effect on the relationship between exposure to domestic violence and use of violence. Also, certainty of being alive at age 25 was found to interact with exposure to community violence to influence use of violence. Specifically, the belief that one would not live to be age 25 operated as a vulnerability mechanism. The findings of this study best supported the compensatory model as one conceptualization of use of violence. / Master of Science

This prospective longitudinal study evaluated the effect of prenatal cocaine exposure (PCE) on executive functioning in 5- and 7-year-old children. In total, 154 pregnant cocaine users, identified by urine toxicology and structured interviews, were matched to 154 nonusers. Children were assessed by certified masked evaluators, and caregivers were interviewed by experienced staff during home visits. In approximately 90% of the surviving sample tested at ages 5 and 7 years, structural equation modeling demonstrated that an increased head circumference at birth (adjusted for gestation) significantly predicted better performance on executive functioning, and that PCE was indirectly related to executive functioning through its significant negative effect on head circumference at birth. At age 5 years, quality of environment also predicted executive functioning, and the R2 for the total model was 0.24. At 7 years, caregiver functioning predicted quality of environment, which in turn was positively related to executive functioning, and girls had better executive functioning. The total model at age 7 years accounted for 30% of the variance in executive functioning.

The effects of developmental lead (Pb2+) exposure on the anxiolytic-like effect of diazepam (5.0 mg/kg IP) and 8-OH-DPAT (0.3 mg/ kg IP) were studied. Wistar dams were exposed to 250 ppm lead acetate in drinking water during pregnancy. Control rats were derived from dams that consumed tap water, and had no exposure to Pb2+ afterwards. Male offspring were tested at the age of 12 weeks. We studied the anxiolytic-like effect of diazepam and 8-OH-DPAT in an elevated plus maze device and the Vogel conflict test. Diazepam in doses of 5.0 mg/kg IP significantly increased the percentage of time spent on open arms in control rats being without effect in Pb2+-exposed animals. 8-OH-DPAT 0.3 mg/kg IP increased the percentage of time spent on open arms in both experimental groups (control and Pb2+ but the anxiolytic-like effect was much more pronounced in Pb2+-intoxicated animals. The benzodiazepine anxiolytic diazepam produced a significant effect in the Vogel conflict test in control rats. A 5.0 mg/kg dose of those drugs caused a significant increase in the number of electric shocks rats received. In the ontogenetically Pb2+-exposed rats diazepam also augmented the number of shocks accepted, but this effect was much less pronounced than in control animals. Conversely, 8-OH-DPAT at doses of 0.3 mg/kg IP was without effect in both tested groups as far as the anticonflict effect is concerned. The results of the present report demonstrated that exposure to Pb2+ during pregnancy induced hypersensitivity to 5-HT1A agonist mediated anxiolytic-like effect but attenuated that of benzodiazepine (diazepam).

The authors analyzed data from a national sample to examine the relationships between blood concentrations of selected volatile organic compounds (VOCs) and the assessment scores of neurobehavioral evaluation tests. They calculated summary statistics to describe blood concentrations of 30 VOCs. For instance, the 95th percentiles were as follows: 1, 1, 1-trichloroethane, 0.799 μg/l; 1, 4-dichlorobenzene, 11.081 μg/l; benzene, 0.476 μg/l; and toluene, 0.281 μg/l. For 1, 4-dichlorobenzene, benzene, dibromochloromethane, and trichloroethene, a blood level higher than the 95th percentile was associated with a poorer neurobehavioral assessment score than was a blood level up to the 95th percentile. The authors found a linear relationship between blood toluene concentration and the Serial Digit Learning Test score. The findings suggest that exposure to certain VOCs may result in poor neurobehavioral performance. The study was exploratory and precludes a conclusive statement, so further investigation is warranted.